Involvement of adenosine in depression of synaptic transmission during hypercapnia in isolated spinal cord of neonatal rats

Abstract

Adenosine is one of the most important neuromodulators in the CNS, both under physiological and pathological conditions. In the isolated spinal cord of the neonatal rat in vitro, acute hypercapnic acidosis (20% CO 2 , pH 6.7) reversibly depressed electrically evoked spinal reflex potentials. This depression was partially reversed by 8-cyclopentlyl-1,3-dimethylxanthine (CPT), a selective A 1 adenosine receptor antagonist. Isohydric hypercapnia (20% CO 2 , pH 7.3), but not isocapnic acidosis (5% CO 2 , pH 6.7), depressed the reflex potentials, which were also reversed by CPT. An ecto-5 -nucleotidase inhibitor did not affect the hypercapnic acidosis-evoked depression. An inhibitor of adenosine kinase, but not deaminase, mimicked the inhibitory effect of hypercapnic acidosis on the spinal reflex potentials. Accumulation of extracellular adenosine and inhibition of adenosine kinase activity were caused by hypercapnic acidosis and isohydric hypercapnia, but not isohydric acidosis. These results indicate that the activation of adenosine A 1 receptors is involved in the hypercapnia-evoked depression of reflex potentials in the isolated spinal cord of the neonatal rat. The inhibition of adenosine kinase activity is suggested to cause the accumulation of extracellular adenosine during hypercapnia.

Adenosine and inosine release during hypoxia in the isolated spinal cord of neonatal rats

“…However, the exposure of OGD for 10 min increased the levels of adenosine and inosine regardless of the presence or absence of FA. We have previously reported that hypercapnia causes the release of adenosine by inhibiting the activity of adenosine kinase in the rat spinal cord (Otsuguro et al ., 2006; 2009). In the present study, we found that the extracellular level of inosine was also increased by exposure (10 min) to hypercapnia (20% CO 2 ).…”

An adenosine kinase inhibitor, ABT-702, inhibits spinal nociceptive transmission by adenosine release via equilibrative nucleoside transporters in rat

“…The hemisected spinal cord preparation with lumber spinal nerve roots was fashioned as previously described (Otsuguro et al, 2006;2011), placed in a bath, and superfused (3 ml/min) with artificial cerebrospinal fluid (ACSF) at 27 ± 2°C. The composition of the ACSF was as follows (mM): NaCl 138, KCl 3.5, CaCl 2 1.25, MgCl 2 1.2, NaHCO 3 21, NaH 2 PO 4 0.6, and glucose 10.…”

Effect of Carbon Dioxide on Calcitonin Gene‐Related Peptide Secretion From Trigeminal Neurons

“…Primary cultures of trigeminal ganglia were used to investigate the cellular effects of 100% CO 2 on CGRP secretion from trigeminal neurons under conditions that either allowed or prevented extracellular acidosis. The effects of extracellular versus intracellular pH changes mediated by CO 2 on CGRP secretion and intracellular pH and calcium levels were determined by allowing PCO 2 to change while controlling extracellular pH, a condition termed isohydric hypercapnia 25‐27 …”

“…The goal of this study was to determine the effects of CO 2 exposure on trigeminal neurons and particularly, on CGRP secretion. We utilized a novel system originally reported by Farley and Adler 34 to study extracellular versus intracellular pH changes caused by CO 2 exposure and their effects on CGRP secretion, by allowing PCO 2 to change while controlling extracellular pH, a condition termed isohydric hypercapnia 25‐27 . Using this system, we demonstrated that CO 2 exposure under isohydric conditions prevented increases in CGRP secretion caused by chemical depolarization, capsaicin, or NO.…”